Ridgway, D., Sopata, M., Burneckis, A., Jespersen, L., & Andersen, C. (2010). Clinical efficacy and safety of once-daily dosing of a novel, prolonged-release oral morphine tablet compared with twice-daily dosing of a standard controlled-release morphine tablet in patients with cancer pain: A randomized, double-blind, exploratory crossover study. Journal of Pain and Symptom Management, 39(4), 712–720.

To compare the safety and efficacy of a once-daily dose of a new formulation of morphine sulfate—abuse-deterrent, prolonged-release erodible-matrix (ADPREM) morphine sulfate—to the safety and efficacy of a twice-daily dose of standard controlled-release morphine

During a run-in period of three days, clinicians determined each patient's effective dose of the study drug. Throughout the study, immediate-release morphine was available for breakthrough pain. The study drug was titrated to provide a level of pain relief characterized by four or fewer episodes of breakthrough pain per day and a level of pain intensity that was acceptable (this level was undefined). Treatment periods were two weeks long. In a crossover trial, patients received either the study drug, once daily, or controlled-release morphine twice daily. In diaries patients recorded daily all medications used, number of breakthrough episodes, and pain ratings. Clinicians evaluated adverse events.

• The sample was composed of 34 patients.
• Mean patient age was 57.5 years. Age range was 42–81 years.
• Of all patients, 36.8% were female and 63.2% were male.
• The most common cancer types in the sample were lung, breast, and rectal cancer.

• Multisite
• Outpatient
• Italy

Randomized phase 2 double-blind crossover study

• Eleven-point numeric rating scale, to measure pain intensity
• Drug-metabolite concentration in plasma

The pattern of treatment-related adverse events was the same for both treatments. The fixed dose determined during the run-in period was 30–210 mg/day. Authors noted no differences between treatments in regard to breakthrough pain episodes or use of rescue medication. Average pain intensity ratings were similar for both treatments.

The efficacy and side effects associated with a once-daily dose of ADPREM morphine sulfate were similar to those associated with twice-daily doses of controlled-release morphine. Studies that include larger samples are warranted.

• The study had a small sample, with fewer than 100 participants.
• Authors did not provide a standard definition of the term acceptable pain.

For some patients, the ability to control pain by using fewer pills daily may be a significant consideration. This study provides evidence that supports the efficacy and safety of a once-daily ADPREM formulation of morphine.